Autosomal dominant polycystic kidney disease (ADPKD) is a leading cause of renal failure for which there is no known cure, prompting intensive research to uncover the causes of pathogenesis. Disease-specific cystogenesis is characterized by perturbations in the polarized phenotype and function of renal epithelial cells. The gene mutated in the majority of ADPKD cases encodes polysystin-1, but the mechanisms leading to alterations in ADPKD cell polarity and function remain obscure. Recently, polycystin-1 has been found in a complex with the essential epithelial cell adhesion molecule E-cadherin. This finding is particularly significant since mutations at the PKD1 locus result in the loss of E-cadherin and basolateral targeting machinery from the plasma membrane of disease cells. Together the new studies suggest that disruption of a multimeric complex involving polycystins. E-cadherin and other essential components specifying cell polarity triggers a pathologic cascade leading to altered epithelial cell phenotype and function. Numerous cellular functions are affected in ADPKD, many of which might be explained by alterations ensuing from aberrant E-cadherin-polycystin-1 interactions in the disease. Combined cellular, morphological and biochemical strategies are proposed to elucidate the molecular assemblies of E-cadherin and polysystin-1 in normal and ADPKD cells and to establish a cause-and-effect relationship between possible altered assembly and cellular phenotype. The loss of cell surface E-cadherin elicits changes in the basolateral transport machinery that are associated with perturbations in Golgi morphology and the accumulation of basolateral cargo in the Golgi. Therefore, a more detailed analysis of the coordinate control mechanisms is warranted. Planned studies will utilize combined light and electron microscopy to determine whether Golgi-to-basolateral membrane transport is impaired due to changes in vesiculation, cytoskeletal translocation and/or signal transduction. The combined strategies will identify important coordinate control mechanisms governing renal epithelial cell function and offer an understanding as to how these are subverted in ADPKD.